在形黑色素瘤中对PD-1阻断的高响应率
Zeynep Eroglu1,2, Jesse M Zaretsky1, Siwen Hu-Lieskovan1
1University of California Los Angeles, Los Angeles, California, USA.
Nature
|January 11, 2018
概括
晚期脱质黑色素瘤患者对PD- 1/ PD- L1阻断疗法的反应显著. 这种罕见的黑色素瘤亚型因突变率高和免疫细胞透而受益于免疫治疗.
科学领域:
- 癌症学
- 免疫学
- 皮肤病学
背景情况:
- 乳性黑色素瘤是一种罕见的亚型,其特征是密集的肌层,化学抵抗性和UV诱导的DNA损伤.
- 它通常缺乏可操作的突变,
研究的目的:
- 评估在晚期脱质黑色素瘤中编程细胞死亡1 (PD-1) 或PD- L1连接体免疫检查点阻塞疗法的疗效.
- 研究与治疗反应相关的基因组和免疫类型特征.
主要方法:
- 用PD-1/ PD- L1抗体治疗的60名晚期脱毛瘤患者的分析.
- 瘤的整体外体测序以确定突变.
- 免疫组织化学评估PD-L1表达和免疫细胞透.
主要成果:
- 在70%的患者 (42/ 60) 中观察到客观的瘤反应,32%的患者达到完全反应 (19/ 60).
- 发现了高突变负载和频繁的NF1突变 (14/17).
- 结核性黑色素瘤在瘤包膜中表达了较高的PD- L1, 与增加的CD8+T细胞密度相关.
结论:
- 患有晚期脱质黑色素瘤的患者从PD- 1/ PD- L1阻断治疗中获得了显著的临床益处.
- 这种疗效可能归因于高突变负担和因PD- L1表达而受到限制的先前适应性免疫反应.
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